Document Detail

Apoptotic DNA fragmentation factor maintains chromosome stability in a P53-independent manner.
MedLine Citation:
PMID:  16619042     Owner:  NLM     Status:  MEDLINE    
DNA fragmentation factor (DFF)/caspase-activated DNase (CAD) is responsible for DNA fragmentation, a hallmark event during apoptosis. Although DNA fragmentation is an evolutionarily conserved process across species, its biological function is not clearly understood. In this study, we constructed cell lines expressing a mutant ICAD (inhibitor of CAD) protein that is resistant to caspase cleavage and therefore constantly binds to DFF/CAD and inhibits DNA fragmentation. We found that irradiation of these cells led to increased chromosome aberrations and aneuploidy when compared with their parental controls. The increased chromosome instability is observed irrespective of cellular P53 status, suggesting that the effect of DFF/CAD is independent of P53. Inhibition of apoptotic DNA fragmentation resulted in increased clonogenic survival of irradiated cells and a delay in removal of cells with DNA damages induced by radiation, an effect similar to that in cells with p53 mutations. Consistent with DFF/CAD's effect on clonogenic survival, tumors established from cells deficient in DNA fragmentation showed enhanced growth in nude mice. Therefore, our results suggest that DFF/CAD plays an important and P53-independent role in maintaining chromosome stability and suppressing tumor development.
B Yan; H Wang; H Wang; D Zhuo; F Li; T Kon; M Dewhirst; C-Y Li
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2006-04-17
Journal Detail:
Title:  Oncogene     Volume:  25     ISSN:  0950-9232     ISO Abbreviation:  Oncogene     Publication Date:  2006 Aug 
Date Detail:
Created Date:  2006-08-31     Completed Date:  2006-09-28     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  England    
Other Details:
Languages:  eng     Pagination:  5370-6     Citation Subset:  IM    
Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA.
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MeSH Terms
Annexin A5 / metabolism
Apoptosis / genetics*
Apoptosis Regulatory Proteins
Cell Division
Cell Line, Tumor
Chromosomal Instability
Chromosome Aberrations*
DNA Fragmentation*
Deoxyribonucleases / metabolism
Flow Cytometry
Tumor Suppressor Protein p53 / metabolism*
Reg. No./Substance:
0/Annexin A5; 0/Apoptosis Regulatory Proteins; 0/Proteins; 0/Tumor Suppressor Protein p53; 0/caspase-activated DNase inhibitor; EC 3.1.-/Deoxyribonucleases; EC 3.1.-/caspase-activated deoxyribonuclease

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